tbuckley/cabot-search huggingface dataset:
Bosutinib (BOS) in newly diagnosed chronic myeloid leukemia (CML): Gastrointestinal (GI), liver, effusion, and renal safety characterization in the BFORE trial.
Authors: Jorge E. Cortes, Dragana Milojkovic, Carlo Gambacorti-Passerini, Valentin García-Gutierrez, Michael J. Mauro, Eric Leip, Simon Purcell, Andrea Viqueira, Tim H. Brümmendorf
Journal: Journal of Clinical Oncology (2022)

7049 Background: Efficacy and safety of BOS vs imatinib (IMA) in patients (pts) with newly diagnosed chronic phase CML was assessed in the phase 3 BFORE trial. Here we characterize the safety profile of BOS after 5 yrs follow-up, with a focus on GI, liver, effusion and renal treatment-emergent adverse events (TEAEs). Methods: Pts who received ≥1 dose of BOS (n=268) or IMA (n=265) 400 mg/d in BFORE were included. Adverse events (AEs) of special interest were analyzed by selecting prespecified MedDRA terms to generate TEAE clusters. Final database lock: June 12, 2020. Results: Median duration of treatment (Tx) was 55 mo for pts receiving BOS or IMA; respective median (range) dose intensity was 393.6 (39–583) vs 400.0 (189–765) mg/d. Any grade TEAEs occurred in 98.9% and 98.9% of BOS- vs IMA-treated pts. Most common newly occurring TEAEs (any grade) after 12 mos were increased lipase (9.0%) with BOS, and diarrhea (8.3%) with IMA. In BOS- vs IMA-treated pts, 25.4% vs 14.3% had AEs leading to permanent Tx discontinuation; the majority discontinued in yr 1 (14.2% vs 10.6%). Most frequent AEs leading to discontinuation were increased ALT (overall, 4.9%; yr 1, 4.5%) with BOS vs thrombocytopenia (overall, 1.5%; yr 1, 1.5%) with IMA. GI, liver, effusion and renal TEAEs, respectively, occurred in 79.9%, 44.0%, 6.0% and 10.4% (maximum grade 3/4 [G3/4]: 9.0%, 26.9%, 1.1% and 2.2%) of BOS- vs 61.5%, 15.5%, 2.3% and 9.8% (G3/4: 1.1%, 4.2%, 0.4% and 0.8%) IMA-treated pts. One grade 5 renal TEAE occurred in the BOS arm and was not considered related to Tx. Cumulative rates per Tx yr are shown in the Table. Most common GI TEAEs were diarrhea (BOS vs IMA: 75.0% vs 40.4% [G3/4: 9.0% vs 1.1%]) with BOS, and nausea (37.3% vs 42.3% [G3/4: 0% vs 0%]) with IMA. In both arms, the most common liver, effusion and renal TEAEs, respectively, were increased ALT and/or AST (34.0% vs 8.3% [G3/4: 22.0% vs 2.3%]), pleural effusion (5.2% vs 1.9% [G3/4: 0.7% vs 0.4%]) and increased blood creatinine (6.7% vs 8.3% [G3/4: 0.4% vs 0.4%]). GI, liver, effusion and renal TEAEs infrequently led to Tx discontinuation (1.9%, 7.8%, 0.7% and 0.7% vs 1.1%, 0.8%, 0% and 0.4%). Conclusions: The safety profiles of BOS and IMA in BFORE were distinct, with no new safety signals identified after 5 yrs follow-up. Onset of TEAEs occurred primarily during yr 1 (eg, GI and liver), with an increased incidence of some TEAEs (eg, effusion and renal) in later yrs. Discontinuations due to AEs generally occurred early into Tx, with few due to GI, liver, effusion and renal AEs. These safety results support the use of first-line BOS as a standard of care in pts with CP CML. Clinical trial information: NCT02130557. [Table: see text]
The impact of an oncology-specific shared savings agreement.
Authors: Edward Thompson, Alexa Hospodar, Sarah McLarty, Sabah Pervez, Heeseon Yeon, Kevin Hastings, Robert Cullum, Christopher Junk, Ujwal Sapkota, Allendre Mcgovern-Siembab, Lady Perez, Patricia Angelica, Namrata Jeshang, William Cavers, Melissa Johlie, Shirisha Reddy, Rogelio A. Brito, Elisea Avalos-Reyes, Kjel Andrew Johnson, Tracy Grunsfeld
Journal: Journal of Clinical Oncology (2022)

1536 Background: In response to rising healthcare costs, several innovative payment strategies have emerged to improve the value and efficiency of healthcare spending. One of these strategies is a shift from volume-based to value-based care (VBC), resulting in the introduction of alternative payment models, innovative provider contracting and new value frameworks. The purpose of this study is to evaluate the impact of a VBC arrangement on total cost of care for chemotherapy patients, specifically cancer-related drug costs, daily hospital inpatient admissions and emergency room visits. Methods: This is a cohort study of chemotherapy patients, in a single state, enrolled in a large national insurer from January 18, 2021, to September 30, 2021. Oncology patients were divided into two groups; the study group consisted of chemotherapy patients receiving care in a VBC arrangement; the control group consisted of chemotherapy patients receiving care at oncology practices not engaged with the insurer in a VBC agreement. The following levers were employed to improve value: digital symptom tracking, biosimilar or lower-cost drug options and NCCN regimen concordance. We defined cancer-related drug costs as the sum of allowed costs paid for medical and pharmacy claims during the study period. Additionally, we averaged the cost per hospital inpatient day and emergency room visit and compared these by group. Results: This study included 1,574 patients, 733 patients in the study group and 841 in the control group. A reduction of 5.1% (a difference of $441) in cancer-related drug costs per member per treatment month (PMPTM) was observed among patients in the study group. Patients in the study group reported 27.8% fewer inpatient days resulting in a savings of $194 PMPTM. Similarly, patients in the study group reported 70.0% fewer emergency room visits resulting in a savings of $59 PMPTM. Conclusions: In this study, chemotherapy patients participating in a shared savings VBC spent less on cancer-related drug costs, hospital inpatient days and emergency room visits through three value levers. Further studies are needed to assess if these results are similar all types of healthcare coverage and to what degree additional value levers further reduce costs. Additionally, the long-term health outcomes of these patients should be assessed.
Outcomes and prognostic factors in patients with HER2-positive metastatic breast cancer with brain metastasis.
Authors: Izzet Dogan, Inci Kizildag Yirgin, Selnur Ozkurt, Kamuran Ibıs, Sezai Vatansever, Pinar Saip, Adnan Aydiner
Journal: Journal of Clinical Oncology (2022)

e14002 Background: Breast cancer is the most common malignancy in females. Brain metastasis is a poor prognostic factor in breast cancer. Brain metastasis can develop in about half of the HER2- positive metastatic breast cancer patients. The study was aimed to determine outcomes and prognostic factors in HER2 positive metastatic breast cancer patients who had brain metastasis. Methods: We evaluated the HER2-positive metastatic breast cancer patients with brain metastasis between 2008 and 2018. Data of the patients were recorded retrospectively. Kaplan Meier and Cox regression analysis were used for survival analysis and prognostic factors. Results: Eighty-three patients were included in the study. The median age was 49 (range, 25-76). Thirty-two (38.6%) patients had de-novo metastatic disease at diagnosis. The most common histopathological type was invasive ductal carcinoma (88.4%). The estrogen receptor and progesterone receptor positivity ratios were 42.2% and 28.9%, respectively. At the beginning of brain metastasis, the median number of extra-cranial metastasis was 2 (range, 0-4). The most common extra-cranial metastasis sites were bone (63.9%), liver (41%), and lung (34.9%), respectively. Twenty-eight patients (41.8%) had solitary brain metastasis. The median size of brain metastasis was 16 mm (range, 5-63) at diagnosis. All patients had treated with trastuzumab-based chemotherapy, 29 patients (34.9%) TDM-1, and 73 patients (88%) lapatinib+capesitabine combination. Seventeen patients (20.5%) had undergone craniotomy, and 82 patients (98.8%) received brain radiotherapy. The patients also received hormonotherapy (41%) and bisphosphonates (56.6%). At a median follow-up of 36 months (range 5.9-177.7) from beginning metastasis, the median overall survival was 34.9 months (95% CI, range 24.6-45.2). In multivariate analysis, age at diagnosis (p = 0.005), presence of five and over brain metastasis (p = 0.016), the number of chemotherapy used with trastuzumab (p = 0.017), and receiving three different HER2-targetted therapy (p = 0.032) were statistically significant for overall survival. However, size of brain metastasis (p = 0.091), lung metastasis (p = 0.428), liver metastasis (p = 0.338), bone metastasis (p = 0.132), and hormone positivity of tumor (p = 0.238) were not. Conclusions: Real-life outcomes of HER2-positive breast cancer patients with brain metastases were presented in this study. We showed that age at diagnosis, number of brain metastasis, number of chemotherapy received with trastuzumab, and had received three different HER2 targetted therapy was prognostic factors for overall survival.
STRIvE-01: Phase I study of EGFR806 CAR T-cell immunotherapy for recurrent/refractory solid tumors in children and young adults.
Authors: Catherine Michelle Albert, Navin R. Pinto, Mallory Taylor, Ashley Wilson, Stephanie Rawlings-Rhea, Stephanie Mgebroff, Christopher Brown, Catherine Lindgren, Wenjun Huang, Kristy Seidel, Prabha Narayanaswany, Vicky Wu, Erin R. Rudzinski, Nicholas A. Vitanza, Juliane Gust, Rebecca Alice Gardner, Michael C. Jensen, Julie R. Park
Journal: Journal of Clinical Oncology (2022)

2541 Background: The epidermal growth factor receptor (EGFR) is a cell surface tyrosine kinase receptor associated with cell proliferation and differentiation. EGFR expression and activating mutations are associated with aggressive neoplastic disease, chemotherapy resistance, and increased metastatic potential. Published data and EGFR immunohistochemistry (IHC) performed on tissue microarrays indicate that 15-40% of pediatric solid tumors (ST) express EGFR. The unique EGFR monoclonal antibody (mAb) 806 selectively binds to an epitope that is conformationally hidden when EGFR is tethered but revealed when tethering is perturbed as occurs with EGFR overexpression, truncation, or through extra-cellular domain missense mutations. Methods: Children and young adults (CYA) with EGFR-expressing recurrent/refractory (R/R) ST were enrolled on a Phase 1 trial to examine the safety and feasibility of administering autologous chimeric antigen receptor (CAR) T cells derived from autologous T cells genetically modified to express a second generation EGFR806-specific scFV-IgG4hinge-CD28tm/cyto-4-1-BB-zeta and EGFRt tracking/suicide contract. All subjects received lymphodepleting chemotherapy with fludarabine and cyclophosphamide prior to the administration of cryopreserved CAR T cells a the prescribed dose level. The biologically effective dose (BED) or maximum tolerated dose was determined based upon observed toxicity through day 28 from initial CAR-T infusion and using a 3+3 statistical design. Results: Eleven subjects (n=10 evaluable, age range 9-25, median 18) were enrolled and received either dose level (DL) 1 (0.5 x 10 6 CAR-T/kg, n=4) or DL2 (1 x 10 6 CAR-T cells/kg, n=7). CAR T were manufactured successfully in all subjects. Most common toxicities were fatigue, tumor-related pain and cytokine release syndrome (n=2, maximum CTCAE grade 1). Dose limiting toxicity of CTCAE grade 4 transaminase level and hyperbilirubinemia occurred at DL2 (n=1). Maximum circulating CAR-T expansion was 29.66 cells/uL (range 0.05-29.66 cells/uL) with median persistence of 28 days (range 0-90). Two subjects on DL1 and one subject on DL2 demonstrated mixed response on day 28 and tolerated additional CAR T infusion without dose limiting toxicity. Conclusions: EGFR806 directed CAR-T cells have an acceptable toxicity profile in CYA with R/RST and demonstrate anti-tumor activity in some patients. Additional analyses are ongoing to identify biomarkers of response and toxicity. Clinical trial information: NCT03618381.
Clinical utility of immunotherapy hyperprogressive genes in hepatocellular carcinoma patients.
Authors: Run Wang, Luyan Lou, Zhaoxia Guo, Yanrui Zhang, Yun Zhang, Feng Lou, Shanbo Cao, Huina Wang
Journal: Journal of Clinical Oncology (2022)

e16126 Background: Hepatocellular carcinoma (HCC) is the most common liver malignancy associated with poor prognosis. With the rapid development of systematic therapy for liver cancer, immunotherapy has been widely used in therapy of liver cancer. Hyperprogression of tumor is a phenomenon of accelerated tumor growth, which occurs in patients with liver cancer and other solid tumors receiving systematic treatment, and is mainly related to immunotherapy hyperprogression genes. However, it is still unclear about the genes of immune hyperprogression in HCC patients. Therefore, we studied the molecular characteristics of HCC patients, including the genes related to immunotherapy hyperprogression. Methods: From June 2019 to August 2021, 102 patients with HCC were inculded in this study. Matched tumor/normal DNA from HCC patients (N = 102) were analyzed by whole exome sequencing (WES) or Acornmed panel with 808 cancer-related genes. Results: Overall, 86.3% (88/102) patients exhibited genetic alterations. TP53 (50%), TERT (23%), CTNNB1 (18%) and KMT2C (14%) were the most commonly mutated genes in HCC. In addition, 8.9% patinets harbored at least one immunotherapy hyperprogressive gene mutations, including CCND1 (7%), FGF19 (6%), FGF3 (5%), FGF4 (5%) and MDM4 (2%). In addition, CCND1 and FGF19 were frequently mutated genes in patients with liver cancer, ranking ninth and tenth, respectively. Compared with the TCGA data, there was no significant difference in immunotherapy hyperprogressive genes (25% vs 32.3%, p = 0.18). Interesting, CCND1, FGF19, FGF3 and FGF4 mutations occurred simultaneously in most patients and were mutually exclusive with MDM4 (p = 0.057). Conclusions: This study contributes to understand the molecular characteristics of patients with HCC, which will be useful to guide immunotherapy and promote the clinical management in this population. Furthermore, the study suggested that both Chinese and Western populations should pay attention to immunotherapy hyperprogression genes in immunotherapy selection.
Neutropenia and neutropenic fever with polatuzumab vedotin for diffuse large B-cell lymphoma: Meta-analysis of randomized clinical trials.
Authors: Varsha Gupta, Vinit Singh, Farhan Khalid, Hussam Eltoukhy, Trishala Meghal
Journal: Journal of Clinical Oncology (2022)

e19576 Background: Polatuzumab vedotin (POLA) is an antibody–drug conjugate composed of an anti-CD79b monoclonal antibody conjugated by a protease-cleavable linker to monomethyl auristatin E, a microtubule inhibitor. POLA has shown efficacy in patients with relapsed or refractory Diffuse large B-Cell lymphoma (DLBCL) and recently shown better progression free survival in previously untreated DLBCL as well. We conducted a meta-analysis of randomized controlled trials (RCTs) to determine the relative risk of neutropenia and febrile neutropenia associated with use of POLA regimens for DLBCL. Methods: We conducted a systematic search at PUBMED, EMBASE, and meeting abstracts as per PRISMA guidelines from 2010 until December 2021. Randomized controlled trial utilizing POLA for DLBCL were included. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I 2 value. All statistical analyses were performed with Review Manager Version 5.4. Results: A total of 1073 patients from 3 RCT (1 Phase III and 2 Phase II Studies) were included in this study. The study arm used POLA-R-CHP (Rituximab, Cyclophosphamide, Doxorubicin, Prednisone), POLA-Rituximab, and POLA-BR (Bendamustine-Rituximab). The control arm used R-CHOP, Pinatuzumab-R, and BR respectively The overall incidence of neutropenia was 31.54% in POLA Group vs 32.94% in control group with RR 0.99 (95% CI: 0.69 – 1.42, P=0.97, I 2 =16%) whereas grade 3-4 neutropenia incidence was 29.24 vs 30.82 with RR 0.95 (95% CI: 0.79 – 1.16, P=0.65, I 2 =2%). The overall febrile neutropenia incidence was 12.87% in Polatuzumab group vs 7.90% in the control group with RR 1.62 (95% CI: 1.12 – 2.35, P = 0.01, I 2 =0%). Conclusions: Our study demonstrated that there was no statistical difference in risk ratio of any grade neutropenia (including grade 3-4) in both the arms. However, there was significantly increased risk of febrile neutropenia among patients who received Polatuzumab vedotin based treatment compared to those who did not. Further studies and long term follow up are necessary to define the actual relation and definitive incidence.[Table: see text]
Improving advanced directive completion rates on an inpatient oncology unit using internal medicine resident participation: A quality improvement study.
Authors: Matthew Doran Bloom, Kelsey Pan, Edward De Leo, Ellery Altshuler
Journal: Journal of Clinical Oncology (2022)

e18636 Background: A written advanced directive (AD) allows patients to indicate their preferences for medical care should they ever lose the ability to make their wishes known. This may take the form of a living will or designation of a healthcare surrogate. AD completion rates remain poor on inpatient oncology units, with only 20-40% of patients having an AD. This is despite the fact nearly all cancer patients (95%) believe discussing ADs is an important issue. It has recently been shown that nearly 87% of cancer patients would support a policy in which admitting physicians offered to have a conversation regarding ADs. The goal of our project was to increase the percentage of patients with documented ADs on our inpatient oncology unit from 30% to 50% using the participation of internal medicine residents. Our secondary objective was to initially assess resident knowledge, confidence and skills with AD discussions. Methods: We carried out a prospective QI project in which we first calculated the percentage of consecutive patients on our inpatient oncology unit with documented ADs. After providing educational materials and delivering AD forms to the resident workroom to increase accessibility, we again calculated the percentage of consecutive patients with documented ADs. We also initially surveyed residents about their knowledge, comfort levels, and barriers to having AD discussions with patients. Results: Pre-intervention, 15 out of 50 (30%) consecutive patients on our inpatient oncology unit had documented ADs. Post-intervention, 13 of 27 (48%) consecutive patients in our oncology unit had documented ADs. Most residents felt their knowledge of ADs was average (46.88%, n = 15) or good (28.13%. n = 9). When asked about comfort in filling out ADs with patients, most responded as average (28.13%, n = 9) or poor (28.13%, n = 9). The main barrier to completing ADs was lack of time (25%, n = 20) followed by lack of knowledge (25%, n = 8) and not feeling the responsibility (12.5%, n = 4). Most residents were interested (65.53%, n = 21) or maybe interested (28.13%, n = 9) in further teaching on ADs. Conclusions: Our study showed that AD completion rates on an inpatient oncology unit can be improved using the participation of internal medicine residents. This was done through a standardized approach of housestaff offering to discuss ADs on admission after they had received short small group teaching sessions on AD discussions. Furthermore, we identified that most internal medicine residents had average or poor comfort in initiating advanced care discussions, but were interested in obtaining further knowledge to help discuss ADs with patients.
Efficacy and safety of QL1706, a novel dual immune checkpoint blockade containing a mixture of anti-PD1 IgG4 and anti-CTLA4 IgG1 antibodies, for advanced cervical cancer: Cohort data from a phase 1b trial.
Authors: Jihong Liu, Naifu Liu, Danbo Wang, Dapeng Li, Cheng Fang
Journal: Journal of Clinical Oncology (2022)

5535 Background: Anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and anti-programmed cell death 1 (PD-1) antibodies have synergistic effect. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies produced by a single cell line. QL1706 showed promising anti-tumor activity in multiple solid tumors. Here we reported the cervical cancer cohort data from the phase 1b trial of QL1706 (NCT05171790). Methods: Eligible patients had a pathologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, with recurrent or metastatic, immunotherapy-naive disease at the time of enrollment. Patients were required to have ≥one lesion measurable by RECIST v1.1 and disease that had relapsed after a first-line, platinum-based regimen. Patients were included regardless of PD-L1 expression status at baseline. Patients received intravenous QL1706 5.0 mg/kg q3w (i.e., recommended phase 2 dose, defined in a phase 1a trial), for up to 24 months. The primary endpoint was confirmed overall response rate (ORR) per RECIST v1.1 by investigator. The secondary endpoints included disease control rate, duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, etc. Results: As of Dec 31, 2021, totally 53 patients with cervical cancer were enrolled (median age, 52 years [range 33-72]). Median follow-up was 5.6 months. Most patients (45 [85%]) had ECOG performance status of 1. Histological breakdown was squamous cell carcinoma (44 [83%]) and adenocarcinoma (nine [17%]). 33 (62%) patients had received one prior chemotherapy, 20(38%) patients had received ≥two prior chemotherapy. The confirmed ORR was 28% (95% CI 17%-42%; 15 patients), including one (2%) complete response and 14 (26%) partial response, with median duration of response not reached (95% CI 2.8 months-not estimable). Disease control was observed in 29 (55%; 95% CI 40%-68%) patients. Median PFS was 4.2 months (95% CI 1.7-6.9), and 6-month PFS rate was estimated as 37% (95% CI 24%-51%). Treatment-related adverse events (TRAE) were observed in 40 (75%) patients. Nine (17%) experienced grade ≥3 TRAE. The most common TRAE were rash (eight [15%]), hyperthyroidism (eight [15%]), and pyrexia (seven [13%]). Three (6%) patients suffered TRAE leading to dose discontinuation. The immune-related TRAE and serious TRAE were observed in 28 (53%) and eight (15%) patients, respectively. Conclusions: QL1706 demonstrated promising and durable clinical activity, with favorable tolerability in patients with recurrent and/or metastatic cervical cancer. Further investigations in this setting are continuing. Clinical trial information: NCT05171790.
Racial parity in rectal cancer treatment and outcomes within an integrated healthcare system.
Authors: Hyunjee V. Kwak, Diana S. Hsu, Andrew Chae, Jeffrey Douaiher, Ching-Kuo Chang
Journal: Journal of Clinical Oncology (2022)

e15538 Background: This study evaluates survival outcomes of rectal adenocarcinoma patients treated at a large, integrated health system and whether there are differences in survival based on race. Methods: We conducted a retrospective study of patients at Kaiser Permanente Northern California (KPNC) who were treated between 2010-2019. Self-reported racial ethnic groups included Caucasian, African American, Hispanic, Asian, and Other. Kaplan Meier and Cox regression analyses were used to evaluate differences in race, age, stage, and treatment utilization in relation to overall survival. Results: A total of 3,589 patients were diagnosed with rectal adenocarcinoma from 2010-2019. There was a significant difference between race groups in stage at the time of diagnosis (p &lt; .001) with more African Americans having localized disease (58.4%) compared to Hispanics (45.5%). Overall survival was longest for African American at 70.9 months but shortest for Hispanic at 60.6 months (p = 0.007). Hispanic patients were more likely to be male, younger, and with nodal disease. Conclusions: This study identified racial parity in survival outcomes for rectal cancer patients who were treated at a large, integrated healthcare system where patients have equal access to care. Improvement in outreach and screening should be tailored to the ethnic groups at higher risk for earlier age and more advanced disease at presentation.